Solid forms of berberine ursodeoxycholate and compositions and methods thereof

Abstract

The invention generally relates to solid forms of berberine ursodeoxycholate, and to pharmaceutical compositions, and methods of preparation and therapeutic use thereof. In particular, the invention relates to solid forms of berberine ursodeoxycholate and pharmaceutical compositions thereof useful in treating and/or preventing various diseases or disorders, including metabolic disorders, heart diseases, neurodegenerative diseases and liver diseases.

The invention claimed is: 
     
       1. A method for preparing a solid form of berberine ursodeoxycholate, which is Form A, having an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ values selected from the group consisting of: 7.06, 7.34, 8.79, 9.47, 11.94, 14.17, 15.50, 16.54 and 16.780 (±0.2°), wherein the Form A of berberine ursodeoxycholate has the formula: 
       
         
           
           
               
               
           
         
         the method comprising:
 forming a mixture of a crystalline and/or amorphous form of berberine ursodeoxycholate with a co-solvent of an organic solvent and H 2 O; 
 stirring the mixture at room temperature; 
 filtering the mixture to obtain a filter cake; 
 washing the filter cake with distilled water; and 
 removing water to obtain Form A of berberine ursodeoxycholate. 
 
       
     
     
       2. The method of  claim 1 , wherein the organic solvent is EtOH. 
     
     
       3. The method of  claim 2 , wherein the EtOH: H 2 O (v/v) is from about 1:5 to about 1:30. 
     
     
       4. The method of  claim 3 , comprising removing water until the water content is about 10% (v/v) or less to obtain Form A of berberine ursodeoxycholate. 
     
     
       5. The method of  claim 4 , wherein the mixture is stirred at room temperature for about 3 to about 7 hours.